Hypothyroidism, also known as underactive thyroid, is a condition in which the thyroid gland does not produce enough thyroid hormones. These hormones influence how the body uses energy, and when levels are low, many processes throughout the body can slow down. Common symptoms include fatigue, weight gain, cold intolerance, depression, constipation, weakness, brittle toenails and fingernails, and dry, thinning hair, among others.

According to the National Institutes of Health, in the United States, 5% of people aged 12 or older have hypothyroidism. Approximately 5% of people are thought to have the condition but have not been diagnosed. In most cases, symptoms are mild. Hypothyroidism can affect people of any age. Infants can be born with congenital hypothyroidism, and it can occur in adults from various causes. The condition is more common in women than in men, and in individuals over age 60.

While there is no cure for hypothyroidism, with appropriate treatment, thyroid hormone levels can usually be normalized. Lifelong treatment, however, is typically necessary.

The thyroid, a small butterfly-shaped gland at the front of the neck, produces and secretes two hormones—80% is thyroxine (T4) and 20% is triiodothyronine (T3)—that help regulate the body’s metabolism and affect the function of organs throughout the body. Thyroid hormones play a role in regulating heart rate, breathing, heat production, digestion, weight, and more. When thyroid hormone levels are low, many body processes slow down, resulting in a number of symptoms, which may include cold sensitivity, fatigue, weight gain, constipation, and slowed heart rate, among others.

The thyroid is regulated by the pituitary gland, a pea-sized gland located at the base of the brain. The pituitary secretes thyroid-stimulating hormone (TSH), which stimulates the thyroid to secrete thyroid hormones. The pituitary’s secretion of TSH is regulated by the hypothalamus, a brain region located above the pituitary that secretes thyrotropin-releasing hormone (TRH).

There are two types of hypothyroidism:

• Primary hypothyroidism, which occurs due to conditions (such as damage or inflammation) that affect the thyroid gland itself. Primary hypothyroidism makes up about 99% of all cases.
• Central hypothyroidism, which occurs due to problems that affect the pituitary gland’s secretion of TSH (sometimes called secondary hypothyroidism) and/or the hypothalamus’s production of TRH (sometimes called tertiary hypothyroidism). In central hypothyroidism, the thyroid gland is not adequately stimulated to produce thyroid hormones, resulting in hypothyroidism.

When hypothyroidism occurs it children, it is classified into one of two types:

• Congenital hypothyroidism, when the condition is present at birth
• Acquired hypothyroidism, when the condition develops after birth, often due to Hashimoto’s disease (see the section on causes of hypothyroidism below)

Both of these types of hypothyroidism in children may result in primary or central hypothyroidism.

Hypothyroidism occurs when the thyroid does not make enough thyroid hormone.

Primary hypothyroidism has a number of possible causes, including:

• Hashimoto’s disease (also known as Hashimoto’s thyroiditis, chronic autoimmune thyroiditis, and chronic lymphocytic thyroiditis), an autoimmune disorder in which antibodies produced by the immune system attack the thyroid gland, causing damage and inflammation and preventing it from producing adequate levels of thyroid hormones. In the U.S., Hashimoto’s disease is the most common cause of hypothyroidism.
• Surgical removal of all or part of the thyroid (for example, to treat other thyroid disorders such as Graves’ disease, thyroid nodules, or thyroid cancer).
• Radioactive iodine (or radioiodine) therapy, a treatment for hyperthyroidism (including Graves’ disease, the most common cause of hyperthyroidism in the U.S.).
• Radiation therapy to the head and neck (for example, for treating head or neck cancer).
• Other types of thyroiditis (inflammation of the thyroid), including:
  • Postpartum thyroiditis (an autoimmune disorder that occurs within a year of giving birth)
  • Silent (also called painless) thyroiditis, which is characterized by an enlarged thyroid that does not cause pain. It is thought to be an autoimmune disorder.
  • Subacute thyroiditis (also called de Quervain thyroiditis or giant cell thyroiditis), which is characterized by pain over the thyroid (in the front of the neck). It may be caused by a viral infection.
• Too much or too little iodine, a mineral found in certain foods, including dairy products, and iodized salt. Iodine is necessary for proper thyroid function.
• Certain medications, including amiodarone, lithium, tyrosine kinase inhibitors, interferon-alfa, immune checkpoint inhibitors, and antiseizure medications among others.

Central hypothyroidism also has a number of possible causes, including:

• Tumors or cysts that press against the pituitary gland.
• Certain medications, including retinoids, mitotane, and glucocorticoids among others.
• Damage to the hypothalamus and/or pituitary due to radiation therapy,surgery, trauma (traumatic brain injury), inflammation (such as hypophysitis, or inflammation of the pituitary gland), or pituitary apoplexy (a condition caused by a blockage of blood flow to or bleeding into the pituitary)
• Gene variants (also known as mutations) that affect the function of the pituitary or hypothalamus.
• Certain infiltrative diseases, such as sarcoidosis, tuberculosis, and hemochromatosis (a condition in which too much iron builds up in the body, which can lead to damage of various organs such as the liver, heart, and pancreas). Infiltrative diseases are conditions in which abnormal substances are deposited in tissues and organs.

Congenital hypothyroidism, which may be primary or central, occurs when a baby is born with hypothyroidism. Possible causes of congenital hypothyroidism include:

• Failure of the thyroid gland to develop properly (the thyroid may be missing, smaller than normal, or in an abnormal location).
• Gene variants that prevent the thyroid from producing sufficient levels of thyroid hormone.
• Problems with the pituitary gland and/or hypothalamus that affect production of TSH.

Risk factors for hypothyroidism include:

• Being female
• Older age (in particular those over age 60)
• Previous thyroid surgery
• Previous radiation to the thyroid, neck, or chest
• Family or personal history of thyroid disease
• Having Turner syndrome, a genetic disorder that affects females and is characterized by short stature and infertility
• Having Down syndrome, also known as trisomy 21, a genetic disorder that leads to developmental and physical delays
• Having postpartum thyroiditis

Certain autoimmune disorders are associated with hypothyroidism, including:

• Type 1 diabetes
• Lupus
• Rheumatoid arthritis
• Sjogren’s syndrome, a disease characterized by dry eyes and mouth
• Pernicious anemia, a disease in which too few red blood cells are produced due to the body’s inability to absorb vitamin B12
• Celiac disease
• Addison’s disease, also known as primary adrenal insufficiency, a disease in which the adrenal glands do not produce enough cortisol and aldosterone

Symptoms of hypothyroidism may include:

• Fatigue
• Weight gain
• Sensitivity to cold
• Joint or muscle pain
• Dry skin
• Dry, thinning hair
• Brittle nails
• Heavy or irregular menstrual periods
• Infertility
• Slowed heart rate
• Depression
• Constipation
• Hoarseness
• Goiter
• Puffy face, hands, or feet
• Eyebrow thinning
• Slowed speech
• Slowed mental activity and/or memory problems
• Weakness

To diagnose hypothyroidism, your doctor will review your medical history, conduct a physical exam, and order one or more diagnostic tests.

Your doctor may ask you whether you have symptoms, and if you do, when they began and their severity. You may also be asked about medications you take, whether you’ve had thyroid surgery or received radiation therapy to the neck or head (for example, as a cancer treatment), whether you have an autoimmune disorder or a family history of thyroid disease. During the physical exam, your doctor will examine your skin and hair, as well as your neck and thyroid. They will measure your vital signs, including your blood pressure, pulse, and temperature, and may also determine whether you have slowed speech or movement.

Additional tests are necessary to make a diagnosis, including:

• Blood tests to evaluate thyroid function. Typically, initial blood work is done to evaluate TSH levels. In primary hypothyroidism, TSH levels are elevated. If TSH levels are abnormal or if your doctor suspects you might have central hypothyroidism, they will likely order an additional blood test to measure T4 levels.

In the U.S., most newborn babies are screened for hypothyroidism.

With treatment, nearly all cases of hypothyroidism can be completely controlled, and with proper treatment, the majority of your symptoms should resolve.

Thyroid hormone replacement is the standard treatment for hypothyroidism. This treatment replaces the hormones that the thyroid does not produce in sufficient amounts with the goal of normalizing the levels of T4 and TSH.

Thyroid hormone replacement usually involves taking daily doses of levothyroxine, a synthetic form of T4. It is usually taken orally, as a pill, though it is also available in gel capsule and liquid form. These alternative forms may improve absorption of the medication by people who have digestive conditions that impair absorption, such as celiac disease.

Your doctor will determine your initial levothyroxine dose based on several factors, including your weight, age, and pregnancy status, TSH level (or T4 level for those with central hypothyroidism), and the cause of hypothyroidism.

Four to six weeks after starting to take this medication, your doctor will order a blood test to monitor your TSH (or T4) level and make dose adjustments as necessary, based on the test results. Blood work may be necessary every four to six weeks until your doctor determines the appropriate dose, and every six to 12 months thereafter.

Most people will need to take levothyroxine for the rest of their lives. Your dose may need to be adjusted over time as you age, if you gain or lose weight, become pregnant, begin taking medications that interact with levothyroxine, or develop a condition that affects levothyroxine absorption.

When untreated or undertreated, people with severe, long-standing hypothyroidism can develop the most severe type of hypothyroidism, known as myxedema coma. Myxedema coma, a life-threatening condition, is characterized by low body temperature, reduced level of alertness or consciousness, altered mental status (such as disorientation or confusion), swelling throughout the body, difficulty breathing, slowed heart rate, low blood pressure, and low blood sugar, among other symptoms. The condition may be triggered by an infection, heart attack, exposure to cold temperatures, surgery, or sedative medications, in particular opioids. It can also occur in patients who do not take their hypothyroidism medication as prescribed. Myxedema coma is a medical emergency that requires immediate treatment in a hospital.

People with hypothyroidism may also be at increased risk for other complications, including:

• High cholesterol
• Heart disease
• Heart failure
• Infertility
• Pregnancy problems, including miscarriage or having a baby with birth defects
• Carpal tunnel syndrome

The outlook for people with hypothyroidism can vary based on a number of factors, including the timing of diagnosis, whether other health conditions are present, and how closely treatment regimens are followed. Many people do very well once they begin thyroid hormone replacement treatment. In general, lifelong treatment is necessary. To keep the condition under control over the long term, regular monitoring of TSH and other relevant lab levels is necessary.

With timely diagnosis and appropriate treatment, the outlook is good for most people. Untreated or undertreated hypothyroidism, however, can lead to serious outcomes such as myxedema coma, which has a poor outlook with a high mortality rate. Untreated hypothyroidism in infants can result in intellectual disability and other health conditions.

"At Yale, our endocrinologists always strive to stay informed about the most up-to-date and evidence-based approach to the diagnosis and treatment of conditions like hypothyroidism," says Yale Medicine endocrinologist Patricia Peter, MD. "Our providers will work with patients and the rest of their medical team to formulate an appropriate treatment plan that will take into account the individual needs of each patient."